tbuckley/cabot-search huggingface dataset:
Explaining normative–deliberative gaps is essential to dual-process theorizing
Authors: Edward J N Stupple, Linden J Ball
Journal: Behavioral and Brain Sciences (2023)

Abstract We discuss significant challenges to assumptions of exclusivity and highlight methodological and conceptual pitfalls in inferring deliberative processes from reasoning responses. Causes of normative–deliberative gaps are considered (e.g., disputed or misunderstood normative standards, strategy preferences, task interpretations, cognitive ability, mindware and thinking dispositions) and a soft normativist approach is recommended for developing the dual-process 2.0 architecture.
Increasing All-Cause Mortality in US Children and Adolescents—Reply
Authors: Steven H. Woolf, Elizabeth R. Wolf, Frederick P. Rivara
Journal: JAMA (2023)

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Could Bayesian cognitive science undermine dual-process theories of reasoning?
Authors: Mike Oaksford
Journal: Behavioral and Brain Sciences (2023)

Computational-level models proposed in recent Bayesian cognitive science predict both the "biased" and correct responses on many tasks. So, rather than possessing two reasoning systems, people can generate both possible responses within a single system. Consequently, although an account of why people make one response rather than another is required, dual processes of reasoning may not be.
Hedgehog Signaling Pathway is a New Therapeutic Target for Patients with Breast Cancer
Authors: Makoto Kubo, Masafumi Nakamura, Akira Tasaki, Naoki Yamanaka, Hiroshi Nakashima, Masatoshi Nomura, Syoji Kuroki, Mitsuo Katano
Journal: Cancer Research (2004)

Abstract The Hedgehog (Hh) signaling pathway functions as an organizer in embryonic development. Genetic analysis has demonstrated a critical role for the Hh pathway in mammary gland morphogenesis. Disruption of Patched1, a component of the Hh pathway, results in abnormal growth of mammary duct. Recent studies have shown constitutive activation of the Hh pathway in various types of malignancies. However, it remains unclear whether this pathway is activated in human breast cancer. Here, we determined the expression of the components, including Sonic Hh, Patched1, and Gli1, of the Hh pathway by immunohistochemical staining in a series of 52 human breast carcinomas. All of 52 tumors display staining of high intensity for Gli1 when compared with adjacent normal tissue. The nuclear staining ratio of Gli1 correlates with expression of estrogen receptor and histologic type. Exposure to cyclopamine, a steroidal alkaloid that blocks the Hh pathway, suppresses expression of Gli1 and the growth of the Hh pathway-activated breast carcinoma cells. These data indicate that the Hh pathway is a new candidate for therapeutic target of breast cancer.
Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma
Authors: Frank Cichocki, Bin Zhang, Cheng-Ying Wu, Emily Chiu, Abderrahman Day, Roddy S. O’Connor, Dima Yackoubov, Ronit Simantov, David H. McKenna, Qing Cao, Todd E. Defor, Murali Janakiram, Rose Wangen, Zuzan Cayci, Nathaniel Snyder, Akhilesh Kumar, Bartosz Grzywacz, Justin Hwang, Yona Geffen, Jeffrey S. Miller, Joseph Maakaron, Veronika Bachanova
Journal: Science Translational Medicine (2023)

Allogeneic natural killer (NK) cell adoptive transfer has shown the potential to induce remissions in relapsed or refractory leukemias and lymphomas, but strategies to enhance NK cell survival and function are needed to improve clinical efficacy. Here, we demonstrated that NK cells cultured ex vivo with interleukin-15 (IL-15) and nicotinamide (NAM) exhibited stable induction of l -selectin (CD62L), a lymphocyte adhesion molecule important for lymph node homing. High frequencies of CD62L were associated with elevated transcription factor forkhead box O1 (FOXO1), and NAM promoted the stability of FOXO1 by preventing proteasomal degradation. NK cells cultured with NAM exhibited metabolic changes associated with elevated glucose flux and protection against oxidative stress. NK cells incubated with NAM also displayed enhanced cytotoxicity and inflammatory cytokine production and preferentially persisted in xenogeneic adoptive transfer experiments. We also conducted a first-in-human phase 1 clinical trial testing adoptive transfer of NK cells expanded ex vivo with IL-15 and NAM (GDA-201) combined with monoclonal antibodies in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) (NCT03019666). Cellular therapy with GDA-201 and rituximab was well tolerated and yielded an overall response rate of 74% in 19 patients with advanced NHL. Thirteen patients had a complete response, and 1 patient had a partial response. GDA-201 cells were detected for up to 14 days in blood, bone marrow, and tumor tissues and maintained a favorable metabolic profile. The safety and efficacy of GDA-201 in this study support further development as a cancer therapy.
Immune suppressive microenvironment in liver metastases contributes to organ-specific response of immunotherapy in advanced non-small cell lung cancer
Authors: Jia-Yi Deng, Qing Gou, Lingling Yang, Zhi-Hong Chen, Ming-Yi Yang, Xiao-Rong Yang, Hong-Hong Yan, Xue-Wu Wei, Jia-Qi Liu, Jian Su, Wen-Zhao Zhong, Chong-Rui Xu, Yi-Long Wu, Qing Zhou
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background The liver is a frequent site of metastases and liver metastases (LM) correlate with diminished immunotherapy efficacy in non-small cell lung cancer (NSCLC). This study aimed to analyze whether tumor response to immunotherapy differs between pulmonary lesions (PL) and LM in NSCLC and to explore potential mechanisms through multiomics analysis. Methods This observational longitudinal clinical cohort study included patients with NSCLC with LM receiving immunotherapy was conducted to evaluate organ-specific tumor response of PL and LM. We collected paired PL and LM tumor samples to analyze the organ-specific difference using whole-exome sequencing, RNA sequencing, and multiplex immunohistochemistry. Results A total of 52 patients with NSCLC with LM were enrolled to evaluate the organ-specific response of immunotherapy. The objective response rate (21.1% vs 32.7%) and disease control rate of LM were lower than that of PL (67.3% vs 86.5%). One-third of patients showed mixed response, among whom 88.2% (15/17) presented with LM increasing, but PL decreasing, while the others had the opposite pattern (p=0.002). In another independent cohort, 27 pairs of matched PL and LM tumor samples from the same individuals, including six simultaneously collected pairs, were included in the translational part. Genomic landscapes profiling revealed similar somatic mutations, tumor mutational burden, and neoantigen number between PL and LM. Bulk-RNA sequencing showed immune activation-related genes including CD8A , LCK , and ICOS were downregulated in LM. The antigen processing and presentation, natural killer (NK) cell-mediated cytotoxicity and T-cell receptor signaling pathway were enriched in PL compared with LM. Multiplex immunohistochemistry detected significantly lower fractions of CD8 + cells (p=0.036) and CD56 dim+ cells (p=0.016) in LM compared with PL. Single-cell RNA sequencing also characterized lower effector CD8 + T cells activation and NK cells cytotoxicity in LM. Conclusions Compared with PL, LM presents an inferior organ-specific tumor response to immunotherapy. PL and LM showed limited heterogeneity in the genomic landscape, while the LM tumor microenvironment displayed lower levels of immune activation and infiltration than PL, which might contribute to developing precise immunotherapy strategies for patients with NSCLC with LM.
Dual inhibition of BTLA and PD-1 can enhance therapeutic efficacy of paclitaxel on intraperitoneally disseminated tumors
Authors: Wei-Zen Sun, Han-Wei Lin, Wan-Yu Chen, Chung-Liang Chien, Yen-Ling Lai, Jung Chen, Yu-Li Chen, Wen-Fang Cheng
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Expression of immune checkpoints in the tumor microenvironment is one mechanism underlying paclitaxel (PTX) chemoresistance. This study aimed to investigate whether the addition of checkpoint blockade to PTX can improve the therapeutic efficacy against apparently disseminated intraperitoneal tumors. Methods We analyzed the in vivo expression of various immune checkpoints in CD3 + CD8 + cytotoxic T cells from tumor-bearing mice treated with or without PTX and validated the tumor-killing activities of selected checkpoint-expressing T-cell subpopulations ex vivo. The regulation of selected checkpoints was investigated in vitro. The therapeutic effects of inhibition of a targeted checkpoint pathway with antibodies added to PTX therapy were examined. Results CD3 + CD8 + T cells expressed with herpes virus entry mediator (HVEM), programmed cell death 1 (PD-1), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3) in tumor-bearing hosts treated with PTX had effective tumoricidal activities. In addition to PTX and cytokines, B and T lymphocyte attenuator (BTLA) or homologous to lymphotoxin, exhibits inducible expression and competes with herpes simplex virus (HSV) glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT) interacting with HVEM can regulate the expression of PD-1 on CD3 + CD8 + T cells. Interleukin (IL)-15 increased the percentage of HVEM high granzyme B (GZMB) + cells among CD3 + CD8 + T cells, which was suppressed by the BTLA/HVEM signal. LIGHT induced the percentage of HVEM + GZMB + cells but not HVEM high GZMB + cells among CD3 + CD8 + T cells. Expression of IL-15, BTLA, or LIGHT was detected in CD19 + B cells and regulated by damage-associated molecular patterns/Toll-like receptor interactions. In the tumor-bearing hosts treated with PTX, certain proportions of BTLA + B or PD-1 + T lymphocytes were still noted. When dual inhibition of BTLA and PD-1 was added to PTX, the antitumor effects on intraperitoneally disseminated tumors can be significantly improved. Conclusions Dual blockade of BTLA on B cells and PD-1 on cytotoxic T cells may have clinical potential for enhancing the efficacy of PTX in the treatment of tumors with intraperitoneal spread, including epithelial ovarian carcinomas.
Development and external validation of a pretrained deep learning model for the prediction of non-accidental trauma
Authors: David Huang, Steven Cogill, Renee Y. Hsia, Samuel Yang, David Kim
Journal: npj Digital Medicine (2023)

Abstract Non-accidental trauma (NAT) is deadly and difficult to predict. Transformer models pretrained on large datasets have recently produced state of the art performance on diverse prediction tasks, but the optimal pretraining strategies for diagnostic predictions are not known. Here we report the development and external validation of Pretrained and Adapted BERT for Longitudinal Outcomes (PABLO), a transformer-based deep learning model with multitask clinical pretraining, to identify patients who will receive a diagnosis of NAT in the next year. We develop a clinical interface to visualize patient trajectories, model predictions, and individual risk factors. In two comprehensive statewide databases, approximately 1% of patients experience NAT within one year of prediction. PABLO predicts NAT events with area under the receiver operating characteristic curve (AUROC) of 0.844 (95% CI 0.838–0.851) in the California test set, and 0.849 (95% CI 0.846–0.851) on external validation in Florida, outperforming comparator models. Multitask pretraining significantly improves model performance. Attribution analysis shows substance use, psychiatric, and injury diagnoses, in the context of age and racial demographics, as influential predictors of NAT. As a clinical decision support system, PABLO can identify high-risk patients and patient-specific risk factors, which can be used to target secondary screening and preventive interventions at the point-of-care.
Correction: Anti-HVEM mAb therapy improves antitumoral immunity both in vitro and in vivo, in a novel transgenic mouse model expressing human HVEM and BTLA molecules challenged with HVEM expressing tumors
Journal: Journal for ImmunoTherapy of Cancer (2023)

Correction: Anti-HVEM mAb therapy improves antitumoral immunity both in vitro and in vivo, in a novel transgenic mouse model expressing human HVEM and BTLA
The values and risks of an Intergovernmental Panel for One Health to strengthen pandemic prevention, preparedness, and response
Authors: Alexandre Hobeika, Maxime Henri Tibault Stauffer, Timothée Dub, Wim van Bortel, Martin Beniston, Salome Bukachi, Gian Luca Burci, Lisa Crump, Wanda Markotter, Ludovico Pasquale Sepe, Enrichetta Placella, Benjamin Roche, Oumy Thiongane, Zhanyun Wang, Frédérique Guérin, Esther van Kleef
Journal: The Lancet Global Health (2023)
X‐Ray Nanothermometry of Nanoparticles in Tumor‐Mimicking Tissues under Photothermia
Authors: Rosalía López‐Méndez, Javier Reguera, Alexandre Fromain, Esraa Samy Abu Serea, Eva Céspedes, Francisco Jose Teran, Fangyuan Zheng, Ana Parente, Miguel Ángel García, Emiliano Fonda, Julio Camarero, Claire Wilhelm, Álvaro Muñoz‐Noval, Ana Espinosa
Journal: Advanced Healthcare Materials (2023)

Temperature plays a critical role in regulating body mechanisms and indicating inflammatory processes. Local temperature increments above 42 °C are shown to kill cancer cells in tumorous tissue, leading to the development of nanoparticle-mediated thermo-therapeutic strategies for fighting oncological diseases. Remarkably, these therapeutic effects can occur without macroscopic temperature rise, suggesting localized nanoparticle heating, and minimizing side effects on healthy tissues. Nanothermometry has received considerable attention as a means of developing nanothermosensing approaches to monitor the temperature at the core of nanoparticle atoms inside cells. In this study, a label-free, direct, and universal nanoscale thermometry is proposed to monitor the thermal processes of nanoparticles under photoexcitation in the tumor environment. Gold-iron oxide nanohybrids are utilized as multifunctional photothermal agents internalized in a 3D tumor model of glioblastoma that mimics the in vivo scenario. The local temperature under near-infrared photo-excitation is monitored by X-ray absorption spectroscopy (XAS) at the Au L
Global prospective case series of ERCPs using a single-use duodenoscope
Authors: Marco J. Bruno, Torsten Beyna, David Carr-Locke, Prabhleen Chahal, Guido Costamagna, Benedict Devereaux, Marc Giovannini, Mahesh K. Goenka, Christopher Khor, James Lau, Gary May, V. Raman Muthusamy, Sandeep Patel, Bret T. Petersen, Douglas K. Pleskow, Isaac Raijman, D. Nageshwar Reddy, Alessandro Repici, Andrew S. Ross, Divyesh V. Sejpal, Stuart Sherman, Uzma D. Siddiqui, Christopher Ziady, Joyce A. Peetermans, Matthew J. Rousseau, Adam Slivka
Journal: Endoscopy (2023)

Background The first commercialized single-use duodenoscope was cleared by the US Food and Drug Administration in December 2019. Data regarding endoscopic retrograde cholangiopancreatography (ERCP) using a single-use duodenoscope are needed on a broader range of cases conducted by endoscopists with varying levels of experience in a wide range of geographic areas. Methods 61 endoscopists at 22 academic centers in 11 countries performed ERCP procedures in adult patients aged ≥ 18. Outcomes included ERCP completion for the intended indication, rate of crossover to a reusable endoscope, device performance ratings, and serious adverse events (SAEs). Results Among 551 patients, 236 (42.8 %) were aged &gt; 65, 281 (51.0 %) were men, and 256 (46.5 %) had their procedure as an inpatient. ERCPs included 196 (35.6 %) with American Society for Gastrointestinal Endoscopy complexity of grades 3–4. A total of 529 ERCPs (96.0 %) were completed: 503 (91.3 %) using only the single-use duodenoscope, and 26 (4.7 %) with crossover to a reusable endoscope. There were 22 ERCPs (4.0 %) that were not completed, of which 11 (2.0 %) included a crossover and 11 (2.0 %) were aborted cases (no crossover). Median ERCP completion time was 24.0 minutes. Median overall satisfaction with the single-use duodenoscope was 8.0 (scale of 1 to 10 [best]). SAEs were reported in 43 patients (7.8 %), including 17 (3.1 %) who developed post-ERCP pancreatitis. Conclusions In academic medical centers over a wide geographic distribution, endoscopists with varying levels of experience using the first marketed single-use duodenoscope had good ERCP procedural success and reported high performance ratings for this device.
Carbon Nitride‐Based siRNA Vectors with Self‐Produced O<sub>2</sub> Effects for Targeting Combination Therapy of Liver Fibrosis via HIF‐1α‐Mediated TGF‐β1/Smad Pathway
Authors: Ming‐Xuan Liu, Li Xu, Yu‐Ting Cai, Ruo‐Jia Wang, Ying‐Ying Gu, Yan‐Chao Liu, Yu‐Jin Zou, Yong‐Mei Zhao, Jing Chen, Xiao‐Ling Zhang
Journal: Advanced Healthcare Materials (2023)

Hypoxia is an important feature, which can upregulate the hypoxia-inducible factor-1α (HIF-1α) expression and promote the activation of hepatic stellate cells (HSCs), leading to liver fibrosis. Currently, effective treatment for liver fibrosis is extremely lacking. Herein, a safe and effective method is established to downregulate the expression of HIF-1α in HSCs via targeted delivery of VA-PEG-modified CNs-based nanosheets-encapsulated (VA-PEG-CN@GQDs) HIF-1α small interfering RNA (HIF-1α-siRNA). Due to the presence of lipase in the liver, the reversible release of siRNA can be promoted to complete the transfection process. Simultaneously, VA-PEG-CN@GQD nanosheets enable trigger the water splitting process to produce O2 under near-infrared (NIR) irradiation, thereby improving the hypoxic environment of the liver fibrosis site and maximizing the downregulation of HIF-1α expression to improve the therapeutic effect, as demonstrated in liver fibrosis mice. Such combination therapy can inhibit the activation of HSCs via HIF-1α-mediated TGF-β1/Smad pathway, achieving outstanding therapeutic effects in liver fibrosis mice. In conclusion, this study proposes a novel strategy for the treatment of liver fibrosis by regulating the hypoxic environment and the expression of HIF-1α at lesion site.
Prediction of metastatic pheochromocytoma and paraganglioma: a machine learning modelling study using data from a cross-sectional cohort
Authors: Christina Pamporaki, Annika M A Berends, Angelos Filippatos, Tamara Prodanov, Leah Meuter, Alexander Prejbisz, Felix Beuschlein, Martin Fassnacht, Henri J L M Timmers, Svenja Nölting, Kaushik Abhyankar, Georgiana Constantinescu, Carola Kunath, Robbert J de Haas, Katharina Wang, Hanna Remde, Stefan R Bornstein, Andrzeij Januszewicz, Mercedes Robledo, Jacques W M Lenders, Michiel N Kerstens, Karel Pacak, Graeme Eisenhofer
Journal: The Lancet Digital Health (2023)

Pheochromocytomas and paragangliomas have up to a 20% rate of metastatic disease that cannot be reliably predicted. This study prospectively assessed whether the dopamine metabolite, methoxytyramine, might predict metastatic disease, whether predictions might be improved using machine learning models that incorporate other features, and how machine learning-based predictions compare with predictions made by specialists in the field.
Correction: UTX inactivation in germinal center B cells promotes the development of multiple myeloma with extramedullary disease
Authors: Ola Rizq, Naoya Mimura, Motohiko Oshima, Shuji Momose, Naoya Takayama, Naoki Itokawa, Shuhei Koide, Asuka Shibamiya, Yurie Miyamoto-Nagai, Mohamed Rizk, Yaeko Nakajima-Takagi, Kazumasa Aoyama, Changshan Wang, Atsunori Saraya, Ryoji Ito, Masanori Seimiya, Mariko Watanabe, Satoshi Yamasaki, Tatsuhiro Shibata, Kiyoshi Yamaguchi, Yoichi Furukawa, Tetsuhiro Chiba, Emiko Sakaida, Chiaki Nakaseko, Jun-ichi Tamaru, Yu-Tzu Tai, Kenneth C. Anderson, Hiroaki Honda, Atsushi Iwama
Journal: Leukemia (2023)
A Cyclodextrin‐Based pH‐Responsive MicroRNA Delivery Platform Targeting Polarization of M1 to M2 Macrophages for Sepsis Therapy
Authors: Ni Ding, Gangjian Luo, Huiting Li, Chengyuan Xing, Yuanji Gao, Wenjie Xi, Weijie Wu, Dan Wang, Lei Zheng, Yang Kang, Xinjin Chi
Journal: Advanced Healthcare Materials (2023)

The mortality rate of sepsis remains high despite improvements in the diagnosis and treatment of sepsis using symptomatic and supportive therapies, such as anti-infection therapy and fluid resuscitation. Nucleic acid-based drugs have therapeutic potential, although their poor stability and low delivery efficiency have hindered their widespread use. Herein, it is confirmed that miR-223 can polarize proinflammation M1 macrophages to anti-inflammation M2 macrophages. A pH-sensitive nano-drug delivery system comprising β-cyclodextrin-poly(2-(diisopropylamino)ethyl methacrylate)/distearoyl phosphoethanolamine-polyethylene glycol (β-CD-PDPA/DSPE-PEG) is synthesized and developed to target M1 macrophages and miR-223 is encapsulated into nanoparticles (NPs) for sepsis treatment. NPs/miR-223 demonstrated in vitro pH responsiveness with favorable biosafety, stability, and high delivery efficiency. In vivo studies demonstrate that NPs/miR-223 are preferentially accumulated and retained in the inflammation site, thereby reducing inflammation and improving the survival rate of mice with sepsis while exhibiting ideal biosafety. Mechanically, NPs/miR-223 regulates macrophage polarization by targeting Pknox1 and inhibiting the activation of the NF-κB signaling pathway, thereby achieving an anti-inflammatory effect. Collectively, it is demonstrated that the miRNA delivery vector described here provides a new approach for sepsis treatment and accelerates the advancement of nucleic acid drug therapy.